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The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs.
Neurology. 2005 Apr 26; 64(8):1397-403.Neur

Abstract

BACKGROUND

Extrapyramidal signs (EPS) are common in Alzheimer disease (AD) and increase in prevalence as AD advances. The neuropathologic substrate responsible for EPS in AD remains to be fully characterized.

METHODS

Subjects had a clinical diagnosis of AD confirmed by neuropathologic examination. EPS during life were documented by clinical methods assessing bradykinesia, cogwheel rigidity, rest tremor, and parkinsonian gait. Subjects with EPS and previous neuroleptic exposure were excluded. Twenty-eight subjects were in the EPS group and 104 subjects were without EPS. Neuron loss, alpha-synuclein (ASYN)-labeled pathology, and tau-labeled pathology in the substantia nigra were measured using semiquantitative techniques such that higher scores represented increased pathologic burden.

RESULTS

Presence of nigral ASYN-labeled pathology was more common (50 vs 28.9%; p < 0.05) in the EPS group than in those without EPS. There was more nigral neuron loss in the EPS group (1.50 vs 1.11 in no-EPS group; p < 0.05). Tau-labeled burden was not different by group comparisons; however, EPS onset at later stages of dementia severity was associated with increased tau-labeled pathology (Kendall tau-B = 0.48, p < 0.01) and this association remained after controlling for dementia severity at death. Additionally, moderate to severe tau burden was more common in the subgroup with "pure AD" (definite AD without other neuropathology) with EPS (81.8%) than cases without EPS (49.0%; p < 0.05). Four subjects with EPS (14.3%) had little to no significant nigral pathologic changes.

CONCLUSIONS

Clinically detected extrapyramidal signs (EPS) in Alzheimer disease (AD) are associated with substantia nigra pathology including alpha-synuclein aggregation, hyperphosphorylated tau accumulation, and neuron loss that may account for the increasing prevalence of EPS as AD progresses. In some cases, limited nigral pathology suggests extranigral factors in the clinical symptoms of EPS.

Authors+Show Affiliations

Department of Neurology, Washington University, St. Louis, MO, USA. jburns2@kumc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15851730

Citation

Burns, J M., et al. "The Pathology of the Substantia Nigra in Alzheimer Disease With Extrapyramidal Signs." Neurology, vol. 64, no. 8, 2005, pp. 1397-403.
Burns JM, Galvin JE, Roe CM, et al. The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs. Neurology. 2005;64(8):1397-403.
Burns, J. M., Galvin, J. E., Roe, C. M., Morris, J. C., & McKeel, D. W. (2005). The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs. Neurology, 64(8), 1397-403.
Burns JM, et al. The Pathology of the Substantia Nigra in Alzheimer Disease With Extrapyramidal Signs. Neurology. 2005 Apr 26;64(8):1397-403. PubMed PMID: 15851730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs. AU - Burns,J M, AU - Galvin,J E, AU - Roe,C M, AU - Morris,J C, AU - McKeel,D W, PY - 2005/4/27/pubmed PY - 2006/1/21/medline PY - 2005/4/27/entrez SP - 1397 EP - 403 JF - Neurology JO - Neurology VL - 64 IS - 8 N2 - BACKGROUND: Extrapyramidal signs (EPS) are common in Alzheimer disease (AD) and increase in prevalence as AD advances. The neuropathologic substrate responsible for EPS in AD remains to be fully characterized. METHODS: Subjects had a clinical diagnosis of AD confirmed by neuropathologic examination. EPS during life were documented by clinical methods assessing bradykinesia, cogwheel rigidity, rest tremor, and parkinsonian gait. Subjects with EPS and previous neuroleptic exposure were excluded. Twenty-eight subjects were in the EPS group and 104 subjects were without EPS. Neuron loss, alpha-synuclein (ASYN)-labeled pathology, and tau-labeled pathology in the substantia nigra were measured using semiquantitative techniques such that higher scores represented increased pathologic burden. RESULTS: Presence of nigral ASYN-labeled pathology was more common (50 vs 28.9%; p < 0.05) in the EPS group than in those without EPS. There was more nigral neuron loss in the EPS group (1.50 vs 1.11 in no-EPS group; p < 0.05). Tau-labeled burden was not different by group comparisons; however, EPS onset at later stages of dementia severity was associated with increased tau-labeled pathology (Kendall tau-B = 0.48, p < 0.01) and this association remained after controlling for dementia severity at death. Additionally, moderate to severe tau burden was more common in the subgroup with "pure AD" (definite AD without other neuropathology) with EPS (81.8%) than cases without EPS (49.0%; p < 0.05). Four subjects with EPS (14.3%) had little to no significant nigral pathologic changes. CONCLUSIONS: Clinically detected extrapyramidal signs (EPS) in Alzheimer disease (AD) are associated with substantia nigra pathology including alpha-synuclein aggregation, hyperphosphorylated tau accumulation, and neuron loss that may account for the increasing prevalence of EPS as AD progresses. In some cases, limited nigral pathology suggests extranigral factors in the clinical symptoms of EPS. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/15851730/The_pathology_of_the_substantia_nigra_in_Alzheimer_disease_with_extrapyramidal_signs_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=15851730 DB - PRIME DP - Unbound Medicine ER -